The goal of the proposed research is to understand the cellular molecular mechanisms by which chemical damage to DNA is converted into a stably inherited mutation. The drug-resistance plasmid, pKM101, causes a striking enhancement of radiation and chemical mutagenesis when present in bacterial screening systems used to detect carcinogens and mutagens. Preliminary work has suggested that the plasmid enhances mutagenesis by enhancing the activity of the hypothesized "error-prone repair" pathway(s) and this relationship will be further examined. The genetics of the system will be characterized by obtaining and studying mutations in both plasmid and chromosomal genes involved in the process. The plasmid-coded protein(s) responsible for the enhancement of mutagenesis will be identified. The effect of the plasmid on branches of both excision and postreplicational-DNA repair will be examined. Restriction fragments of the plasmid, pKM101, will be cloned in a plasmid vector. Results of these studies will be applied to improving the Ames' Salmonella/microsomal screening system. It is hoped that elucidation of the molecular mechanisms of chemical mutagenesis in enteric bacteria will provide a model for similar processes in eucaryotes and will lead to an understanding of the origin of diseases such as cancer.